This invention relates to a composition and method for treating the symptoms associated cognitive and emotional conditions such as those found in attention deficit disorder (ADD), attention deficit/hyper activity disorder (AD/HD), Tourette""s Syndrome, some forms of autism, and other physiological conditions which manifest cognitive or emotional abnormalities.
It has been recognized that a significant number of children are persistently hyperactive and have an attention span so short that they have difficulty in school and in social interactions. For example, such children have difficulty in situations that require sustained attention such as listening to teacher instructions, working on class assignment alone or in groups, and in completing assignments that require concentration. This condition carries over into adulthood, and manifests itself in many ways. For example, various physiological and/or psychological conditions cause symptoms that manifest in low frustration tolerance with temper outbursts, bossiness, stubbornness, insistence that requests be met, mood lability and poor self esteem, among others.
There are no established diagnostic laboratory tests in the clinical assessment of ADHD, as it is not yet clear as to the cognitive deficit responsible for the abnormal mental processing exhibited in ADHD.
For many years, methylphenidate hydrochloride (RITALIN) has been used to treat ADD and/or ADHD. Ritalin is a mild stimulant that has undesirable side effects such as nervousness, insomnia, hypersensitivity, anorexia, nausea, among others. Ritalin and other stimulants also do not relieve the often encountered excessive emotional response as they do not generate the emotional buffering or filtering necessary to delay and attenuate an excessive emotional response.
There are other physiological and/or psychological conditions that cause similar symptoms of uneasiness, restlessness, edginess, difficulty in concentration, recognition and memory deficiency, etc, requiring the use of prescription drugs such as WELLBUTRIN (1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone), which tend to cause side effects. Imipramine, desipramine, nortriptyline, amitriptyalin and cloripramine may also be used to treat symptoms such as associated with ADD/ADHD, excessive emotional response, etc. but these tricyclic drugs follow diverse mechanisms and tend to cause side effects. As these are normally chronic conditions, long term tolerance of the treatment is essential to successfully managing these symptoms. It is difficult for an individual to tolerate daily doses of a drug with even moderate side effects for life, yet that is what is presently required for theses individuals to function in society.
The search continues for a safe, effective and convenient treatment for the symptoms associated with diverse cognitive and emotional symptoms caused by conditions such as ADD and AHDH, for both adults and children, without the disadvantages and side effects found in the existing treatments.
It is an object of the present invention to provide a composition for the treatment and relief of the symptoms associated with conditions such as encountered with ADD or ADHD, and anxiety syndromes/conditions.
It is a further object to provide a method for treating the symptoms associated with various cognitive and/or emotional disorders such as ADD or ADHD.
It is yet another object to provide a method of treating the symptoms described above caused by diverse conditions, that is safe, effective and free of the side effects associated with prior treatments.
These and other objects of the present invention are achieved by a composition comprising at least one butyrate formulated preferably for oral administration, in a pharmaceutically acceptable carrier. Preferably, the butyrate is an alkali or alkaline earth metal salt of nbutyric acid, hereafter collectively termed the xe2x80x9cbutyratexe2x80x9d. An example of the alkali metal salt may be the lithium, sodium or potassium butyrate, the alkaline earth salt may be calcium, magnesium or barium butyrate, or combinations thereof. Certain other butyrates may also be effective such as the ammonium or zinc butyrate, and thus the invention is not limited to those listed above.
The method comprises treating the symptoms of cognitive or emotional disorders, such as those described above relative to ADD/ ADHD, though caused by any of a number of psychological and/or physiological conditions, by administrating an effective amount of a butyrate to a person in need of such treatment.
The invention utilizes one or more alkali metal or alkaline earth metal salts of n-butyric acid in a pharmaceutically acceptable carrier. Preferably, one or more of the lithium, sodium, potassium, calcium, magnesium, zinc and barium butyrate is used.
In a preferred embodiment magnesium butyrate is used, though in another embodiment, a mixture of calcium and magnesium butyrate is used.
In a more preferred embodiment, the composition is formulated with one ore more optional ingredients such as antioxidants, antidepressants, memory promoters/enhancers, various vitamins, nutritional and herbal supplement that can be co-factors or otherwise enhance or synergize with the inventive compound and/or in the inventive treatment method.
The method of the invention comprises the administration of an effective amount of at least one butyrate, whether an alkali metal or alkaline earth metal, ammonium or zinc salt of 4-butyric acid. The salt may be selected from the group consisting of lithium, sodium, potassium, rubidium, cesium, beryllium, zinc, magnesium, calcium, strontium or barium, more preferably, sodium, potassium, magnesium and the calcium salts, most preferably the calcium and magnesium salts.
While any one salt may be used, it may be preferred to use a combination of salts such as a mixture of calcium and magnesium salts of 4-butyric acid, in a ratio of from 10:90 to 90:10 parts calcium to magnesium. More magnesium to calcium is preferred.
Butyric acid is a short claim fatty acid synthesized in the mammary glands. It is an oily liquid that has an unpleasant, rancid odor. It is produced by bacterial fermentation of unabsorbed carbohydrate in the colon and reaches concentrations of up to 20 mM in the colon and feces of animals and man. The other source of butyric acid is in the diet where it is present in low levels in many fruits and vegetables, but the best source is from milk fat, such as in butter, which contains 3-4% butyrate in a complex of glycerides or esters of glycerol butter fat. The calcium and magnesium butyrates apparently have no side effects when taken as a nutritional supplement and are classified as food by the Department of Agriculture. They are known for use as digestive aids and for desensitizing the gastrointestinal tract.
While alkali metal butyrates have been proposed for use in reducing food sensitivity, their use as agents for treating cognitive and emotional problems have not been recognized.
It is believed that the effectiveness of the proposed compounds relies on an increase in gamma amino butyric acid (GABA) in the brain, a well known inhibiting neurotransmitter. Thus, absorption of these compounds is believed to promote transfiguration into GABA, to raise the level of GABA in the brain. It is believed that these butyrates, or derivatives thereof formed in the blood stream, cross the blood brain barrier for conversion into GABA.
Preferably, one or more butyrates are formulated with promoters to enhance transformation to GABA. These may include, but are not limited to pyridoxine 5-phosphate, cyanocobalamin, folic acid, niacin and magnesium, which may be released from magnesium butyrate during the formation of GABA. L-glutamine, 1-phenylalanine, 1-tyrosine and 1-taurine may also be included to promote dopamine, epinephrine, and norepinephrine formation, and to provide a calming effect.
Herbal supplements such as adaptogen including a medicinal mushroom cordyceps sinensis, could be used as it is a known moderator that enhances brain functions that are under active and calms down brain functions that are over active.
Phosphatidyl serine is an agent shown to have positive effects on short term memory and to treat symptoms associated with ADD/ADHD, and is complementary to the inventive composition. Pregnenolone is also a possible choice as a complementary compound, as is ginkgo biloba and/or the flavenols or oligomeric proanthocyanodins, known antioxidants, as well as the plant extract from huperzia serrata, a promoter for developing serotonin receptors on neurons.
Of course, many other compounds and ingredients can be formulated with the inventive compounds to enhance effectiveness or provide complementary beneficial effects in the treatment of cognitive and emotional disorders as discussed above.
The beneficial effects of the butyrate may be obtained by a dose level of about 200 to 3000 mg butyrate per day, preferably by oral supply of tablets containing from 200-1500 mg butyrate per capsule, the dose split into, for example, 2 tablets 3 times per day or 3 tablets, two times per day (500 mg per tablet). Smaller doses at multiple times per day may be preferred.